The p38-MAPK is selectively activated by upstream MAPK kinase (MKK) 3 and MKK6 kinases.82 The major downstream targets of p38-MAPK are protein kinases and transcription factors such as MAPK-activated protein kinase 2 (MK2), mitogen- and stress-activated protein kinase 1 (MSK1), p53, transcription factor ELK1, and activating transcription factor 2 (ATF2).83 The p38-MAPK pathway features a complicated regulation in cancers. The gene discussed is TP53; the disease is cancer.